CANCER RESEARCH

β2-Microglobulin Induces Epithelial to Mesenchymal Transition and Confers Cancer Lethality and Bone Metastasis in Human Cancer Cells

2011-05-09T15:30:00.001-05:00

Bone metastasis is one of the predominant causes of cancer lethality. This study demonstrates for the first time how β2-microglobulin (β2-M) supports lethal metastasis in vivo in human prostate, breast, lung, and renal cancer cells. β2-M mediates this process by activating epithelial to mesenchymal transition (EMT) to promote lethal bone and soft tissue metastases in host mice. β2-M interacts with its receptor, hemochromatosis (HFE) protein, to modulate iron responsive pathways in cancer cells. Inhibition of either β2-M or HFE results in reversion of EMT. These results demonstrate the role of β2-M in cancer metastasis and lethality. Thus, β2-M and its downstream signaling pathways are promising prognostic markers of cancer metastases and novel therapeutic targets for cancer therapy. Cancer Res; 71(7); 2600–10. ©2011 AACR

Recent Advances in Cancer Therapy: An Overview

2010-09-16T11:24:00.000-05:00

Abstract:

The landscape of cancer treatment has dramatically changed over the last four decades. The age when surgery and radiotherapy were the only effective way to fight tumour growth has ended. A complex scenario where the molecular features of tumours seem to be the cornerstone of any therapy is now emerging. Here we provide an overview on the different approaches to cancer treatment. This review will help the reader to acknowledge the pivotal role of some classic cancer therapies, including surgery, radiation, chemotherapy and endocrine therapy, now better understood in the mechanims underpinning their efficacy. Following, we focus on the understanding of the value of systemic treatment and on an up-date on the novel, up-coming therapies of the current targeted therapy age, including new antibodies, small molecules, antiangiogenics and viral therapy. We briefly elaborate, finally, on new biomarkers development and how it should rule and determine the future of therapeutic research in cancer.

Authors: Urruticoechea, A.1; Alemany, R.1; Balart, J.1; Villanueva, A.1; Vinals, F.1; Capella, G.1

Source: Current Pharmaceutical Design, Volume 16, Number 1, January 2010 , pp. 3-10(8)

Bone-Marker Levels

2010-06-28T14:23:00.001-05:00

Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.

Milton S. Hershey Medical Center, Pennsylvania State University Cancer Institute, Hershey, Pennsylvania, USA.

The skeleton is typically the first site of metastasis in patients with prostate cancer, and bone metastases can result in severe bone pain and potentially debilitating fractures. Although bone scans are a reliable means of assessing osteoblastic lesions, tools for monitoring early changes in bone health are lacking. Biochemical markers of bone turnover might fulfill this unmet need.

Correlative studies have suggested that bone-marker levels may have utility in assessing disease progression and response to bone-directed therapy. Elevated levels of the markers, N-telopeptide of type I collagen and bone-specific alkaline phosphatase, are associated with higher rates of death and skeletal-related events in the bone metastasis setting. Marker levels also correlate with response to zoledronic acid treatment, and similar data with the investigational agent, denosumab, are emerging.

Changes in bone-marker levels reflect alterations in skeletal homeostasis and can provide important insights into bone disease progression and response to bone-directed therapy in patients with prostate cancer. More mature data from currently ongoing clinical trials will provide further insight on the utility of marker assessments as an adjunct to established monitoring methods in prostate cancer.

Written by:
Saad F, Lipton A

Effects of distant metastasis and peripheral CA 15-3 on the induction of spontaneous T cell responses in breast cancer patients

2010-01-28T13:04:00.000-06:00

Abstract Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they can be reactivated to IFN-γ producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-γ EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs.

We observed tumor-reactive BM memory T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A*0201-restricted peptides from the tumor-associated antigens MUC1, Hpa16–24 and Hpa183–191 was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific cellular immune responses in the human BM

Christoph Domschke1 , Florian Schuetz1, Nora Sommerfeldt2, Joachim Rom1, Alexander Scharf1, Christof Sohn1, Andreas Schneeweiss1 and Philipp Beckhove2

(1) Department of Gynecology and Obstetrics, University Hospital of Heidelberg, Voßstraße 9, 69115 Heidelberg, Germany
(2) Tumor Immunology Program, Division of Translational Immunology, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany

Epigenetic Profiles Distinguish Malignant Pleural Mesothelioma from Lung Adenocarcinoma

2009-11-24T12:17:00.000-06:00

Cancer Research, 10.1158/0008-5472.CAN-09-1595

Malignant pleural mesothelioma (MPM) is a fatal thoracic malignancy, the epigenetics of which are poorly defined. We performed high-throughput methylation analysis covering 6,157 CpG islands in 20 MPMs and 20 lung adenocarcinomas. Newly identified genes were further analyzed in 50 MPMs and 56 adenocarcinomas via quantitative methylation-specific PCR. Targets of histone H3 lysine 27 trimethylation (H3K27me3) and genetic alterations were also assessed in MPM cells by chromatin immunoprecipitation arrays and comparative genomic hybridization arrays. An average of 387 genes (6.3%) and 544 genes (8.8%) were hypermethylated in MPM and adenocarcinoma, respectively.

Hierarchical cluster analysis showed that the two malignancies have characteristic DNA methylation patterns, likely a result of different pathologic processes. In MPM, a separate subset of genes was silenced by H3K27me3 and could be reactivated by treatment with a histone deacetylase inhibitor alone. Integrated analysis of these epigenetic and genetic alterations revealed that only 11% of heterozygously deleted genes were affected by DNA methylation and/or H3K27me3 in MPMs. Among the DNA hypermethylated genes, three (TMEM30B, KAZALD1, and MAPK13) were specifically methylated only in MPM and could serve as potential diagnostic markers. Interestingly, a subset of MPM cases (4 cases, 20%) had very low levels of DNA methylation and substantially longer survival, suggesting that the epigenetic alterations are one mechanism affecting progression of this disease.

Our findings show a characteristic epigenetic profile of MPM and uncover multiple distinct epigenetic abnormalities that lead to the silencing of tumor suppressor genes in MPM and could serve as diagnostic or prognostic targets. [Cancer Res 2009;69(23):OF1–10]
Yasuhiro Goto1, Keiko Shinjo1,3, Yutaka Kondo1, Lanlan Shen7, Minoru Toyota8, Hiromu Suzuki9, Wentao Gao10, Byonggu An1, Makiko Fujii1, Hideki Murakami1, Hirotaka Osada1,3, Tetsuo Taniguchi5, Noriyasu Usami5, Masashi Kondo4, Yoshinori Hasegawa4, Kaoru Shimokata11, Keitaro Matsuo2, Toyoaki Hida6, Nobukazu Fujimoto12, Takumi Kishimoto12, Jean-Pierre J. Issa7 and Yoshitaka Sekido1,3
Divisions of 1 Molecular Oncology and 2 Epidemiology and Prevention, Aichi Cancer Center Research Institute; Departments of 3 Cancer Genetics and 4 Respiratory Medicine and 5 Division of General Thoracic Surgery, Nagoya University Graduate School of Medicine; 6 Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; 7 Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; 8 Department of Biochemistry and 9 First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan; 10 Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China; 11 Department of Biomedical Sciences, Chubu University, Kasugai, Japan; and 12 Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan

Key Words: DNA methylation • histone H3 lysine 27 trimethylation • malignant pleural mesothelioma • microarray

Lymph node density is a significant predictor of outcome in patients with oral cancer

2009-08-20T11:05:00.000-05:00

BACKGROUND:: The impact of lymph node metastases on prognosis in patients with oral cavity squamous cell carcinoma (OSCC) has been well recognized. However, accurate stratification of risk for recurrence among patients with lymph node metastases is difficult based on the existing staging systems. In the current study, the utility of lymph node density (LND) was evaluated as an alternative method for predicting survival.

METHODS:: Three hundred eighty-six patients who underwent neck dissection were included. The median follow-up was 67 months. Five-year overall survival (OS), disease-specific survival (DSS), and locoregional failure (LRF) rates were calculated using the Kaplan-Meier method. LND (number of positive lymph nodes/total number of excised lymph nodes) and tumor-node-metastasis (TNM) staging variables were subjected to multivariate analysis.

RESULTS:: Using the median (LND = 0.06) as the cutoff point, LND was found to be significantly associated with outcome. For patients with LND 0.06 (P < .001). Similarly, the DSS for patients with LND 0.06 (P < .001). On univariate analysis, pathologic T and N classification, extracapsular spread, and LND were found to be significant predictors of outcome (P < .001). However, on multivariate analysis, LND remained the only independent predictor of OS (P = .02; hazards ratio, 2.0), DSS (P = .02; hazards ratio, 2.3), and LRF (P = .005; hazards ratio, 4.1). LND was also found to be the only significant predictor of outcome in patients receiving adjuvant radiotherapy (P < .05). Within individual subgroups of pN1 or pN2 patients, LND reliably stratified patients according to their risk of failure (P < .05).

CONCLUSIONS:: After surgery for OSCC, pathologic evaluation of the neck using LND was found to reliably stratify the risk of disease recurrence and survival. Cancer 2009. (c) 2009 American Cancer Society.

Gil Z, Carlson DL, Boyle JO, Kraus DH, Shah JP, Shaha AR, Singh B, Wong RJ, Patel SG.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York

Colon cancer screening practices and disclosure

2009-06-22T10:52:00.000-05:00

Colon cancer screening practices and disclosure after receipt of positive or inconclusive genetic test results for hereditary nonpolyposis colorectal cancer.

BACKGROUND:: Patients who receive conclusive genetic test results for hereditary nonpolyposis colorectal cancer (HNPCC) tend to adopt appropriate colorectal cancer screening behaviors and disclose their test results. However, little is known about the disclosure processes or screening behaviors of individuals who receive inconclusive genetic test results. This study compared endoscopy use and disclosure between individuals with positive and inconclusive genetic test results, within a year after results were received.

METHODS:: Individuals with a personal history of cancer and suspected of having HNPCC participated in genetics education and counseling, underwent HNPCC testing, and received genetic test results (GCT) within a prospective cohort study. Demographic, psychosocial, and behavioral data were obtained from questionnaires and interviews completed before and after GCT.

RESULTS:: Index cases with inconclusive genetic test results were less likely to screen within 12 months. Index cases who disclosed test results to children within 6 months were more likely to screen within 12 months, controlling for mutation status. Index cases with inconclusive genetic test results were less likely to share results with a healthcare provider within 6 months. Index cases who disclosed genetic test results to healthcare providers within 6 months were more likely to have endoscopy within 12 months.

CONCLUSIONS:: Genetic test results and disclosure significantly affected colon cancer screening at 12-month follow-up. Interventions to improve adherence to colorectal cancer screening should consider increased education of those receiving inconclusive results and encourage disclosure to healthcare providers and family members. Cancer 2009. Published 2009 by the American Cancer Society.

Dietary and stored iron as predictors of breast cancer risk

2009-05-17T10:17:00.001-05:00

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case-control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co-carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case-control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing Ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16-5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04-6.68, p = 0.02).

In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer
Moore AB, Shannon J, Chen C, Lampe JW, Ray RM, Lewis SK, Lin M, Stalsberg H, Thomas DB.
Department of Public Health and Preventive Medicine, Oregon Health and Sciences University, Portland, OR

Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax

2008-07-10T15:29:00.001-05:00

The thorax is the most frequent extrapelvic location of endometriosis. Thoracic endometriosis is probably responsible for the high rate of recurrent pneumothoraces in females. The goal of the present prospective study was to assess the value of cancer antigen(CA)125 measurement in the detection of endometriosis in order to further enable early and adequate treatment of catamenial pneumothorax.

Between January 2004 and March 2006, 31 females (mean age 32 yrs) underwent pneumothorax surgery. The control group comprised 17 males (mean age 27 yrs), who underwent videothoracoscopic pleural abrasion. Serum CA125 was measured around a menstrual period in females and before surgery in males.

Videothoracoscopically diagnosed endometriosis occurred in 29% of females. The cancer antigen(CA)125 concentration was significantly higher in females with endometriosis compared to disease-free females (76.1 versus 16 U·mL–1). The mean value in males was similar to that observed in disease-free females.

The frequency of thoracic endometriosis-related pneumothorax corresponds to, on average, a third of females presenting with recurrent pneumothorax. Early detection can be achieved with serum cancer antigen 125 measurement and may be helpful in indicating videothoracoscopic surgery.

Neem leaf glycoprotein helps to generate carcinoembryonic antigen specific anti-tumor immune responses utilizing macrophage-mediated antigen presentat

2008-07-07T14:17:00.001-05:00

In an objective to generate effective carcinoembryonic antigen (CEA) specific anti-tumor immune response in Swiss mice, CEA was presented using macrophages with adjuvant help from neem leaf glycoprotein (NLGP). Such vaccination generates significantly higher antibody (IgG2a) and T cell response than immunization protocol without NLGP. NLGP controls the function of both B cells and macrophages by altering the expressions of various regulatory molecules, like, CD19, CD11b, etc. NLGP also directs carcinoembryonic antigen (CEA) vaccination towards Th1 bias, by modulating cytokine secretion. This NLGP-generated anti-CEA immune response would be effective as a vaccine to lyse CEA+ tumors in vitro and in vivo.

ARTICLE

Plasma DNA Is More Reliable than Carcinoembryonic Antigen for Diagnosis of Recurrent Esophageal Cancer

2008-07-07T13:46:00.001-05:00

Background
Carcinoembryonic antigen (CEA) and plasma DNA are known to be elevated in patients with esophageal cancer and are higher in patients with disseminated disease. The sensitivity and specificity of these markers in the diagnosis of recurrent esophageal cancer have not been compared.

Study Design
Plasma DNA was measured using polymerase chain reaction in 45 patients with esophageal cancer and 44 asymptomatic volunteers. The 95th percentile (19 ng /mL) in the volunteers was used to define normal. Thirty-nine patients had localized cancer and underwent resection, and six had disseminated disease at operation. Plasma DNA was measured preoperatively in all patients, with serum Carcinoembryonic antigen (CEA) measured in 31. Plasma DNA was measured sequentially during followup in 21 patients, including 7 who developed recurrence. CEA was measured in 14 of 21 patients who had sequential plasma DNA measured and in 6 of 7 patients with recurrence. CEA levels greater than 5.0 ng/mL were used as cut-off.

Results
Plasma DNA was more sensitive than CEA for detecting unresectable esophageal cancer (100% versus 40%), but it had a lower specificity (22% versus 89%).The positive predictive value (19% versus 40%) and negative predictive value (100% versus 89%) were similar for plasma DNA and serum CEA, respectively.

Plasma DNA was also more sensitive than CEA in detecting recurrent esophageal cancer (100% versus 33%). The specificity and positive predictive values were 100% for both tests, but the negative predictive values were higher for plasma DNA. Plasma DNA rose before there was clinical evidence of recurrence in 67% compared with only 17% for CEA.

Conclusions
Elevated plasma DNA is an extremely reliable indicator of the presence of recurrent disease, and, in the majority of patients, it rises before clinical evidence of recurrence. In contrast, a normal Carcinoembryonic antigen (CEA) should be interpreted cautiously, because it does not exclude recurrent disease.

ARTICLE

Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes

2008-07-07T13:42:00.001-05:00

Background: To investigate the association between tumor markers [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] and clinicopathological parameters and patient outcomes in breast cancer.

Materials and methods: A total of 740 patients with stages I–III breast cancer had preoperative [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] concentrations measured. Univariate and multivariate analyses were used to investigate associations between marker concentration and clinicopathological parameters and patient outcomes.

Results: Among 740 patients, elevated preoperative levels of [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] were identified in 92 (12.4%) and 79 (10.7%) patients, respectively. Tumor size (>5 cm), node metastases (4), and advanced stage (III) were associated with higher preoperative levels. Elevated CA 15-3 and CEA levels were associated with poor disease-free survival (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018, P = 0.015) even in stage-matched analysis. Patients with normal levels of both CA 15-3 and CEA showed better DFS and OS than those with elevated group. In multivariate analysis, age (<35 years), tumor size (>2 cm), node metastases, estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values were independent prognostic factors for DFS.

Conclusion: High preoperative [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] levels may reflect tumor burden and are associated with advanced disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be helpful for predicting outcomes.

PSA-based Screening for Prostate Cancer: How Does It Compare with Other Cancer Screening Tests?

2008-06-30T15:13:00.002-05:00

Context
Despite the substantive societal impact of prostate cancer, the medical community is currently divided on the balance between benefit and harm of screening for prostate cancer using prostate-specific antigen (PSA).

Objective
To examine whether PSA-based screening for prostate cancer meets current guidelines on efficacy and effectiveness for screening, and how it compares with other currently implemented cancer-screening methods.

Evidence acquisition
A literature search was conducted for reviews and individual studies that have examined the performance of screening for colorectal, cervical, breast, and prostate cancer. Each screening method was assessed using the United Kingdom National Screening Committee guidelines. Data on screening test performance (sensitivity, specificity, etc) were extracted from these articles for comparison.

Evidence synthesis
In common with other cancers for which screening is conducted, prostate cancer represents a significant morbidity and mortality burden. The PSA test can be considered “simple” and “safe” within appropriate boundaries. The sensitivity/specificity profile of PSA is not optimal but has clinical validity: Cases missed at screening detected as interval cases do not have a poor outcome. Early prostate cancer intervention can be beneficial for long-term outcomes, although the benefits need to be weighed against the adverse effects of intervention. Early evidence from screening studies also suggests positive stage and grade shifts, although Level 1 mortality data are still awaited. Robust cost-effectiveness data are still lacking, although current evidence suggests that PSA screening may lie within acceptable limits.

Conclusion
Until better markers become available, prostate-specific antigen (PSA) can be regarded as an appropriate screening tool for prostate cancer at a population level.

Exposure to Monoclonal Antibodies

2008-06-23T11:33:00.005-05:00

Excluding those classified as orphan drugs, there are 10 monoclonal antibodies currently used to treat cancer, asthma, or rheumatoid arthritis. Five are composed of various types of humanized immunoglobulin G (IgG) and two of murine IgG. The approved indications include leukemia, metastatic carcinoma of the colon or rectum, squamous cell carcinoma of the head and neck, non-Hodgkin's lymphoma, metastatic breast cancer, and moderate to severe chronic diseases such as asthma and rheumatoid arthritis.

The antineoplastic agents are alemtuzumab (Campath), bevacizumab (Avastin), cetuximab (Erbitux), gemtuzumab ozogamicin (Mylotarg), ibritumomab tiuxetan (Zevalin), panitumumab (Vectibix), tositumomab and iodine 131 (Bexxar), and trastuzumab (Herceptin). The ninth member of this group, rituximab (Rituxan), is also used as an antirheumatic agent.

Exposure of the embryo and fetus should be expected whenever these antibodies are used in pregnancy. Although their molecular weights are very high, two are known to cross the placenta: Rituxan in humans and Herceptin in monkeys. The transplacental passage of the other antibodies has not been studied, but endogenous IgG crosses the placenta. Moreover, the long elimination half-lives ranging from about 2 to 19 days will place these antibodies at the maternal-fetal interface for prolonged periods. Animal reproduction studies have not been conducted with Bexxar, Campath, Erbitux, or Zevalin. Studies in pregnant animals with Herceptin and Rituxan suggested low risk for humans, whereas the suggested risk was higher for Avastin, Mylotarg, and Vectibix.

Bexxar, Campath, Erbitux, Mylotarg, Zevalin, and Rituxan may cause severe, infusion-related toxicity, including hypotension. Although premedication is used to lessen this effect, this toxicity could have deleterious effects on placental perfusion, resulting in harm to the embryo and fetus.

Human pregnancy data are available only for Herceptin and Rituxan. For Herceptin, the human pregnancy experience is limited to five cases, two of which involved first-trimester exposure. Although no congenital malformations were observed, fetal renal toxicity, as evidenced by oligohydramnios or anhydramnios, was observed in three cases. The toxicity might have been caused by inhibition of human epidermal growth factor receptor 2 (HER-2) in the fetal kidneys. The renal toxicity was reversible, and all five infants developed normally. However, there is potential for other toxicity because HER-2 protein expression is high in many embryonic tissues, such as cardiac and neural tissues.

Six pregnancies have been exposed to Rituxan, including two in the first trimester. No structural anomalies were noted, and all infants appeared to be healthy at birth. One had depletion of B lymphocytes, but B-cell counts returned to normal at about 4 months of age. No increase in infectious disease was noted in any of the infants.

Reports of exposure to Bexxar and Mylotarg during pregnancy are unlikely. Bexxar, indicated for non-Hodgkin's lymphoma, contains radioactive iodine and is contraindicated in pregnancy. Mylotarg, a combination of gemtuzumab (IgG4k) conjugated with the cytotoxic antitumor antibiotic calicheamicin, is indicated for the treatment of patients with CD33-positive acute myeloid leukemia in first relapse who are 60 years of age or older. Mylotarg caused significant developmental toxicity at a small fraction of the human dose in the only experimental animal species tested. The therapeutic regimen for Zevalin, another agent for non-Hodgkin's lymphoma, should preclude its use in pregnancy because it includes two radioactive components as well as Rituxan, and the risk to the embryo and fetus appears to be high.

Omalizumab (Xolair), a monoclonal antibody used for moderate to severe persistent asthma, selectively binds to human IgE and has a half-life of 26 days. It has not been studied in animals or humans, but probably crosses the placenta. Reproduction studies in monkeys suggest that the risk in human pregnancy is low, but the human pregnancy experience is limited. In clinical trials, 29 women became pregnant during treatment with Xolair, which was stopped when pregnancy was diagnosed. Among these patients, there were 4 spontaneous abortions (SABs), 3 elective abortions, 11 normal deliveries, and 11 ongoing pregnancies. The number of SABs, all occurring in the first trimester, is within the expected incidence for recognized pregnancies.

A full assessment of the risk of monoclonal antibodies during pregnancy is not possible because of the very limited or absent human pregnancy data, including a lack of long-term evaluation of exposed offspring. Nevertheless, these agents are used for life-threatening diseases and, if indicated, should not be withheld from a pregnant woman—with the exception of Bexxar, Mylotarg, and possibly Zevalin.

GERALD G. BRIGGS, B.PHARM, FCCP

Proenzyme Prostate Specific Antigen for Prostate Cancer Detection: A National Cancer Institute Early Detection Research Network Validation Study

2008-06-13T10:42:00.002-05:00

Purpose
This study evaluated the [-2]proenzyme prostate specific antigen serum marker using a blinded reference specimen set from 3 National Cancer Institute Early Detection Research Network centers from men with an indication for prostate biopsy.

Materials and Methods
Serum was collected before biopsy from 123 men with no prior biopsy or prostate cancer history. Specimens (cancer cases 51%, noncancer controls 49%) were selected equally from the 3 sites, and analyzed for prostate specific antigen, free prostate specific antigen, [-2]proenzyme prostate specific antigen , benign prostate specific antigen and testosterone (Beckman Coulter ACCESS® analyzer).

Results
There was no difference in total prostate specific antigen concentrations (noncancer 6.80 ± 5.20 ng/ml, cancer 6.94 ± 5.12 ng/ml) among the groups. Overall %[-2]proenzyme prostate specific antigen had the greatest area under the curve (AUC 0.69) followed by percent free prostate specific antigen (AUC 0.61). For %[-2]proenzyme prostate specific antigen maximal sensitivity was 60% and specificity was 70%. A logistic regression model combining prostate specific antigen, benign prostate specific antigen, percent free prostate specific antigen, %[-2]proenzyme prostate specific antigen, [-2]proenzyme prostate specific antigen/benign prostate specific antigen and testosterone had an AUC of 0.73. In the 2 to 10 ng/ml prostate specific antigen range %[-2]proenzyme prostate specific antigen and the model had the largest AUC (0.73). The AUC for percent free prostate specific antigen was 0.53. Specificities for %[-2]proenzyme prostate specific antigen, the logistic regression model and percent free prostate specific antigen at 90% sensitivity were 41%, 32% and 18%, and at 95% sensitivity were 31%, 26% and 16%, respectively.

Conclusions
%[-2]proenzyme prostate specific antigen was the best predictor of prostate cancer detection compared to percent free prostate specific antigen, particularly in the 2 to 10 ng/ml total prostate specific antigen range. These findings provide a rationale for broader validation studies to determine whether %[-2]proenzyme prostate specific antigen alone can replace other molecular prostate specific antigen assays (such as percent free prostate specific antigen) for improving the accuracy of prostate cancer early detection. These findings also support the usefulness of well characterized, carefully collected reference sets to evaluate new biomarkers.

Lori J. Sokolla, , , Yinghui Wangc, Ziding Fengc, Jacob Kaganb, Alan W. Partina, Martin G. Sandad, Ian M. Thompsone, † and Daniel W. Chan

ARTICLE

Researchers develop test for ovarian cancer

2008-03-02T10:30:00.004-06:00

Medical researchers say they have developed one of the first early detection tests for ovarian cancer .
Most women suffering from ovarian cancer only learn of their condition when the cancer is in its advanced stages.
Professor Greg Rice from the Women's Cancer Foundation says the test has about a 94 per cent accuracy rate.
However he says it must be at least 99 per cent accurate to attract government subsidies.
Professor Rice says the test measures five blood components.

"It's a different type of blood test - it measures five substances in blood, and has a better diagnostic accuracy, particularly for early stage ovarian cancer ," he said.

"It will probably be in the range of $100 to $200, so yes that's pricey, in one sense.

"If it identifies that you are at risk of ovarian cancer, is it costly? No."

The test will be available within six months.

health, diseases-and-disorders, cancer, medical-research, science-and-technology, scitech-breakthroughs, ovarian-cancer,

From: ABC news in science

Yale test detects early stage ovarian cancer with 99 percent accuracy

2008-02-12T14:04:00.000-06:00

Researchers at Yale School of Medicine have developed a blood test with enough sensitivity and specificity to detect early stage ovarian cancer with 99 percent accuracy.

Results of this new study are published in the February 15 issue of the journal Clinical Cancer Research. The results build on work done by the same Yale group in 2005 showing 95 percent effectiveness of a blood test using four proteins.

“The ability to recognize almost 100 percent of new tumors will have a major impact on the high death rates of this cancer,” said Mor. “We hope this test will become the standard of care for women having routine examinations.”

Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths in the United States and three times more lethal than breast cancer . It is usually not diagnosed until its advanced stages and has come to be known as the “silent killer.”

This new phase II clinical trial led by Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale, included 500 patients; 350 healthy controls and 150 ovarian cancer patients. Mor and colleagues validated the previous research and used a new platform called multiplex technology to simplify the test into one single reaction using very small amounts of serum from the blood. The new platform uses six protein biomarkers instead of four, increasing the specificity of the test from 95 to 99.4 percent. The team looked for the presence of specific proteins and quantified the concentration of those proteins in the blood.

The Early Detection Research Network (EDRN) of the National Cancer Institute (NCI) independently evaluated the results of the test.

“This is the most sensitive and specific test currently available,” said Mor. “Previous tests recognized 15 to 20 percent of new tumors. Proteins from the tumors were the only biomarkers used to test for ovarian cancer. That is okay when you have big masses of tumors, but it is not applicable in very early phases of the tumor. Testing the proteins produced by the body in response to the presence of the tumor as well as the proteins the tumors produce, helped us to create a unique picture that can detect early ovarian cancer.”

Mor and colleagues have begun a phase III evaluation in a multi-center clinical trial. In collaboration with EDRN/NCI and Laboratories Corporation of America (LabCorp), they are testing close to 2,000 patients.

The test is available at Yale through the Discovery to Cure program. Yale has licensed the test to three companies: Lab Corp in the United States, Teva in Israel and SurExam in China.

Other authors on the study included Irene Visintin, Ziding Feng, Gary Longton, David C.Ward, Ayesha B. Alvero, Yinglei Lai, Jeannette Tenthorey, Aliza Leiser, Ruben Flores-Saaib, Herbert Yu, Masoud Azodi, Thomas Rutherford and Peter E. Schwartz.

Citation: Clinical Cancer Research 14 (4) February 15, 2008

Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes.

2008-02-05T12:31:00.002-06:00

BACKGROUND: To investigate the association between tumor markers [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] and clinicopathological parameters and patient outcomes in breast cancer . Materials and methods: A total of 740 patients with stages I-III breast cancer had preoperative CA 15-3 and CEA concentrations measured. Univariate and multivariate analyses were used to investigate associations between marker concentration and clinicopathological parameters and patient outcomes.

RESULTS: Among 740 patients, elevated preoperative levels of CA 15-3 and CEA were identified in 92 (12.4%) and 79 (10.7%) patients, respectively. Tumor size (>5 cm), node metastases (>/=4), and advanced stage (>/=III) were associated with higher preoperative levels. Elevated CA 15-3 and CEA levels were associated with poor disease-free survival (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018, P = 0.015) even in stage-matched analysis. Patients with normal levels of both CA 15-3 and CEA showed better DFS and OS than those with elevated group. In multivariate analysis, age (<35 years), tumor size (>2 cm), node metastases, estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values were independent prognostic factors for DFS.

CONCLUSION: High preoperative CA 15-3 and CEA levels may reflect tumor burden and are associated with advanced disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be helpful for predicting outcomes.

Ann Oncol. 2007 Nov 23

Chemoprevention of breast cancer.

2008-01-29T14:05:00.000-06:00

Trials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced at a late stage in the natural history with prophylactic agents.

About half of the oestrogen receptor positive cases were prevented, but there was no beneficial effect on ER-negative cancers. The current challenge is to find new agents which achieve this or better efficacy but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynaecologic symptoms, and thromboembolic events.

Results for contralateral tumours in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70-80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II) and the other exemestane (MAP.3). New agents are needed, for receptor negative breast cancer and several possibilities are currently under investigation.

John Snow Professor of Epidemiology, Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary’s School of Medicine and Dentistry, University of London, Charterhouse Square, London, EC1M 6BQ, UK, jack.cuzick@cancer.org.uk.

Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head

2007-12-26T16:17:00.001-06:00

BACKGROUND: The differential diagnosis of solid lesions located at the pancreatic head is very important for choosing therapies and setting up surgical tactics. This study was designed to evaluate the clinical significance of combined measurement of multiple serum tumor markers and the application of the receiver-operating characteristic (ROC) curves in the differential diagnosis of solid lesions located at the pancreatic head.

METHODS: The serum levels of CA19-9 , CA242, CA-50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of the pancreatic head and 38 patients with focal chronic pancreatitis in the pancreatic head were measured with ELISA. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum tumor markers were calculated. The ROC curves for the four serum tumor markers were constructed and the area under the curve (AUC) was calculated.

RESULTS: The AUCs of CA19-9 , CA242, CA50 and carcinoembryonic antigen were 0.805, 0.749, 0.738 and 0.705; the PLRs were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71, respectively. Combined measurements increased the diagnostic specificity, and parallel combined testing increased the diagnostic sensitivity.

CONCLUSIONS: Combined measurement of serum tumor markers CA 19-9 , CA 24-2, CA-50 and CEA is valuable in differential diagnosis of solid lesions located at the pancreatic head, and CA19-9 , has the best diagnostic ability. Combined measurements can increase the specificity of diagnosis. Evaluation with the ROC curve is better than the sensitivity or specificity alone and the results are more integrated and objective.

Liao Q, Zhao YP, Yang YC, Li LJ, Long X, Han SM.
Department of General Surgery, Peking Union Medical College Hospital, Beijing 100730, China,Hepatobiliary Pancreat Dis Int. 2007 Dec;6(6):641-5

Cancer Antigens Information

2007-11-12T08:27:00.001-06:00

According to published reports;
CEA: slight to moderate Carcino Embryonic Antigen elevations (rarely above 10 ng/ml) occur in 15-30% of benign diseases of the intestine, the pancreas, the liver and the lungs: liver cirrhosis, chronic hepatitis, pancreatitis, ulcerative colitis, Crohn's disease, and emphysema. Smokers also have elevated CEA values.

CA 15-3: slightly elevated Cancer Antigen 15-3 serum values (up to 50 U/ml) are occasionally found in patients with liver cirrhosis, hepatitis, autoimmune disorders, and benign diseases of the ovary and breast. Non-mammary malignancies in which elevated CA 15-3 assay values have been reported include lung, colon, pancreatic, primary liver, ovarian, cervical, and endometrial.

CA 19-9: even slight cholestasis can lead to clearly elevated Cancer antigen 19-9 serum levels in some cases. Elevated values are also found with a number of benign and inflammatory diseases of the gastrointestinal tract and the liver, as well as in cystic fibrosis. Cancer antigen 19-9 is not sensitive or specific enough to be considered useful as a tool for cancer screening. Its main use is as a tumor marker:
to help differentiate between cancer of the pancreas and bile ducts and other non-cancerous conditions, such as pancreatitis; to monitor a patient's response to pancreatic cancer treatment; and to watch for pancreatic cancer recurrence.

CA 125: slight to moderate elevations have been reported for Cancer Antigen 125 in individuals with non-malignant conditions such as cirrhosis, hepatitis, endometriosis, first trimester pregnancy, ovarian cysts, and pelvic inflammatory disease. Elevations during the menstrual cycle have also been mentioned. Non-ovarian malignancies include cervical, liver, pancreatic, lung, colon, stomach, biliary tract, uterine, fallopian tube, breast and endometrial carcinomas. CA-125 is used to monitor therapy during treatment for ovarian cancer. Cancer Antigen 125 is also used to detect whether cancer has come back after treatment is complete. This test is sometimes used to follow high-risk women who have a family history of ovarian cancer but who do not yet have the disease

CA 72-4: elevated serum values of Cancer Antigen 72-4 can be found in benign illnesses: pancreatitis, cirrhosis of the liver, pulmonary diseases, rheumatic illnesses, gynecological illnesses, benign diseases of the ovaries, ovarian cysts, illnesses of the breast, benign disorders of the gastrointestinal tract.

AFP: as the alpha fetoprotein values rise during regeneration of the liver, moderately elevated values are found in alcohol-mediated liver cirrhosis and acute viral hepatitis, as well as in carriers of HbsAg (hepatitis B antigen).

PSA: an inflammation or trauma of the prostate (e.g. in cases of urinary retention, or following rectal examination, cystoscopy, colonoscopy, transurethral biopsy, laser treatment or ergometry) can lead to Prostate Specific Antigen elevations of varying duration and magnitude. Benign hypertrophy of the prostate is frequently involved: the free PSA dosage helps to clear the matter, with the evaluation of FPSA/PSA quotient.

Free PSA: in patients receiving therapy, particularly hormone withdrawal therapy, the FPSA/PSA quotient cannot be utilized to differentiate prostate hyperplasia from cancer of the prostate.

B2M: rheumatic arthritis, lupus, Crohn's disease, myeloma, chronic lymphoid leukemia can increase results for Beta 2 microglobulin, as does renal failure.

BHCG: elevated HCG concentrations not associated with pregnancy are found in patients with tumors of the germ cells, ovaries, bladder, pancreas, stomach, lungs and liver.

NSE: Neuron Specific enolase concentrations (inf 12 ng/ml) have been found in patients with benign pulmonary diseases and cerebral diseases. Moderate elevations are reported in cerebrovascular meningitis, disseminated encephalitis, spinocerebellar
degeneration, cerebral ischemia and infarction, intracerebral hematoma, head injuries, inflammatory brain diseases, organic epilepsy, schizophrenia, and Jakob-Creutzfeld disease.

Scanning electrochemical microscopy with enzyme immunoassay of the cancer-related antigen CA15-3

2007-10-22T15:06:00.001-05:00

Scanning electrochemical microscopy (SECM) with enzyme immunoassay was applied to detect the cancer related antigen CA15-3 (Ag). In this method, CA15-3 was concentrated and immobilized on a plane substrate via a sandwich method employing two corresponding antibody (Ab captured on a streptavidin-coated substrate and Ab* labeled with horseradish peroxidase (HRP)). In the presence of hydroquinone (H2Q) and H2O2, HRP on the complex of CA 15-3 with Ab and Ab*, Ab–Ag–Ab*, converted H2Q to the electroactive product benzoquinone (BQ) through the HRP-catalyzed reaction. The reduction current of BQ generated by the HRP-catalyzed reaction corresponding to the amount of CA15-3 was monitored and imaged by SECM. With a view of improving the sensitivity of SECM-enzyme immunoassay to meet our objective, Ab–Ag–Ab* was concentrated on the substrate via a microcell. The detection limit of this method was 2.5 U/mL for CA15-3 .

CANCER TOO CLOSE TO HOME

2007-09-29T08:48:00.002-05:00

Lee Biosolutions supports cancer research worldwide. We are very proud to be able to supply several cancer markers to passionate researchers who are trying to find a cure for breast cancer, liver cancer,brain cancer ,pancreatic, there are so many I can't even list here.

Our products include Cancer Antigen 15-3 breast cancer marker, Cancer Antigen 72-4 proposed as a marker for cancers of the ovary, gastrointestinal tract and lung. Cancer Antigen 19-9 primarily used distinguishing pancreatic cancer from pancreatitis and cancer Antigen 125 to name a few.

It kind of hit home for me this year finding out that my sister was diagnosed with breast cancer. Instead of having that long dark brown hair that I remember when we were kids that touched below her belt, it has all fallen out from chemotherapy treatments. She went through all the battery of tests and really had to take charge because as I found out everyone has a different opionin. She knows she made the right decision on the more aggressive treatments but I'll be honest with you, its tough not only for her but for everyone around who loves her.

So I went on line and found the following. Now, I'm not a doctor and you are ultimately responsible for understanding what in the hell is going on but I thought I would share this with you..

"Early stage breast cancer is usually confined to the ducts that transport milk to the nipple during lactation (breast feeding) or to the lobules (small areas of tissue where milk is produced in the breast) and is known as noninvasive cancer. If the cancer is confined to the ducts, it is called ductal carcinoma in situ (DCIS) and if it is confined to the lobules, it is called lobular carcinoma in situ (LCIS). At this stage, the cancer cannot be felt as a lump in the breast, but DCIS can sometimes be detected by mammography.

Invasive stage breast cancer is characterized by a spread of the cancer beyond the ducts or lobules and into the surrounding areas of breast tissue. At this stage, the cancer may be detected through a breast self-exam, by a clinical breast exam performed by a health care professional, or by mammography.

Metastatic stage breast cancer is cancer that has spread (metastasized) to other areas of the body, including nearby lymph nodes. At this stage, treatment requires the combined effort of several specialists, including surgeons, oncologists, and radiologists

There are a variety of laboratory tests that can be performed to diagnose and monitor breast cancer and its treatment. These tests can be broken down into four groups, based on the purpose of testing:

To diagnose: cytology (microscopic examination of cells obtained through fine needle aspiration) and surgical pathology (microscopic examination of tissue sampling via biopsy)

To determine treatment options: evaluation of HER-2/neu gene amplification status, estrogen and progesterone receptor status

To monitor (identify recurrence): CA 15-3 / CA 27.29

To determine genetic risk: examination of mutations that may be present in the BRCA-1 and BRCA-2 genes. "

All this information is from Labtestoneline.org